Type 1 diabetes is an immune-mediated disease in which insulin-producing beta cells are destroyed, resulting in life-long dependence on exogenous insulin. The number of patients being diagnosed is increasing each year, particularly in the very young. Despite advances in glucose monitoring and insulin delivery, there is a compelling need to identify therapies that may safely alter the course of immune mediated beta cell destruction and preserve, and even increase, beta cell function. It is well established that patients with type 1 diabetes are marked by defects in regulatory T cells and or interleukin-2 (IL-2) or its receptor signaling that controls autoimmunity. Transient treatment with low-dose recombinant IL-2 increased regulatory T cell number and induced the persistence of repaired IL-2 responsiveness in diabetic patients. These clinical data strongly support further development of IL-2 based therapy. However, current low-dose rIL-2 therapy has a very short half life with an unwanted increase in several innate immune cells types such as natural killer cells and eosinophils. To obtain ideal outcomes in patients who are mostly young and feel otherwise healthy and have little short term morbidity, we have designed a long-acting IL-2 analog that promises to generate low and stable circulating levels of IL-2 related agonist. The IL-2 analog effectively binds to high affinity trimolecular IL-2R complex but not the intermediate affinity bimolecular IL2R complex (e. g. natural killer cells, eosinophils). Only regulatory T cells and newly activated, previously nave T cells express the high affinity IL2R. While IL-2 is essential for the viability and functional integrity of regulatory T cells, IL-2 is actually a death factor fr newly activated T effector cells. Hence, the innovative drug candidate at low-dose will enable selective stimulation of regulatory T cells and transient or intermittent administration while minimizing negative clinical effects. Importantly, a better efficacy and safety profile has been demonstrated in multiple animal models. The specific aim of this Phase I SBIR proposal is to determine whether twice-weekly treatment with the innovative IL-2 analog for 4 weeks will more effectively restore euglycemia for 14 weeks of follow up than daily treatment of rIL2 for 4 weeks in spontaneous new onset (onset of <48hours) diabetic NOD mice.